May 17, 2022

New Publication from Dr. Cheryl Arrowsmith and Dr. Mathieu Lupien

Graphical abstract from article
Graphical abstract from article.

MBP scientists Dr. Cheryl Arrowsmith and Dr. Mathieu Lupien have co-authored a new Nature article entitled ‘PRMT inhibition induces a viral mimicry response in triple-negative breast cancer.

MBP researchers Dr. Daniel de Carvalho and Dr. Benjamin Haibe-Kains also contributed to the paper, alongside several other collaborators.

Article Abstract
Triple-negative breast cancer (TNBC) is the most aggressive breast cancer subtype with the worst prognosis and few effective therapies. Here we identified MS023, an inhibitor of type I protein arginine methyltransferases (PRMTs), which has antitumor growth activity in TNBC. Pathway analysis of TNBC cell lines indicates that the activation of interferon responses before and after MS023 treatment is a functional biomarker and determinant of response, and these observations extend to a panel of human-derived organoids. Inhibition of type I PRMT triggers an interferon response through the antiviral defense pathway with the induction of double-stranded RNA, which is derived, at least in part, from inverted repeat Alu elements. Together, our results represent a shift in understanding the antitumor mechanism of type I PRMT inhibitors and provide a rationale and biomarker approach for the clinical development of type I PRMT inhibitors.